Effect of endogenous levels of human chorionic gonadotropin (hCG) on glucose and lipid metabolism in male mice

RATNER LD, MARCIAL LOPEZ A, SUAREZ ORTEGA A; ALZAMENDI A; GIOVAMBATTISTA A; SPINEDI E; HUHTANIEMI I; CALANDRA RS; RULLI SB.

Orlando, Florida

Congreso; The Endocrine Society´s 99th Annual Meeting; 2017

endocrine society

Male hypogonadism is characterized by androgen deficiency and infertility. Androgen replacement therapy in prepubertal boys and men induces and maintains normal secondary sexual characteristics, sexual function, and behavior. Conversely, hCG therapy may be used in patients with hypogonadotropic hypogonadism to recover fertility, since hCG treatment stimulates spermatogenesis by inducing androgen production. Because the impact of hCG therapy on metabolic pathways has not been fully investigated, experimental studies on this topic need to be explored. Recent investigations in female mice have shown the impact of the overexpression of hCG on the carbohydrates and lipid metabolism (1). In addition, we have assessed that transgenic male mice overexpressing hCGb subunit (hCGb+) are fertile and have normal plasma testosterone levels, with minor disturbances of the gonadal axis (2). Conversely, males overexpressing a and b subunits of hCG (hCGab+) are infertile and, exhibited high plasma levels of androgens. The aim of this study was to analyze the influence of hCG on both glucose and lipid metabolism in adult transgenic mice. Food intake, body weight (BW) gain and, tryglicerides, cholesterol, glucose, insulin and leptin levels were analyzed. In addition, glucose (GTT) and insulin tolerance tests (ITT) were performed. Finally, pancreas, liver and white adipose tissue histological analyses were performed. Transgenic males from both groups displayed normal plasma levels of insulin, triglycerides and cholesterol. hCG+ mice showed increased serum leptin levels, food intake and BW vs WT mice (p < 0.01). Alterations in the GTT were observed in both groups (p < 0.05), whereas only hCGab+ mice have developed insulin resistance. Hypertrophic white adipose tissue mass was noticed in both transgenic mice, whereas pancreatic and liver cell morphology remained normal. These results indicated that early and chronic hCG exposure induced a clearly disturbed glucose metabolism, although no effect on lipid metabolism appeared. Our study highlights that mainly carbohydrate metabolic aspects in patients under long-term hCG therapy due to hypogonadism, should be carefully monitored.1 J Endocrinol. 2016 230(1):157-69.2 Endocrinology. 2003 144(11):4980-90.